PMID- 21544314
OWN - NLM
STAT- MEDLINE
DCOM- 20111027
LR  - 20181201
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 105
IP  - 6
DP  - 2011 Jun
TI  - Proton pump inhibitors, genetic polymorphisms and response to clopidogrel 
      therapy.
PG  - 933-44
LID - 10.1160/TH10-11-0715 [doi]
AB  - Clopidogrel has become part of the mainstay of therapy for acute coronary 
      syndromes and in patients post stenting. Clopidogrel is a pro drug and is 
      metabolised by liver enzymes, particularly CYP2C19, into its active form. A 
      considerable proportion of patients have a poor response to clopidogrel and this 
      may be due to several factors. Genetic polymorphisms involved in clopidogrel's 
      absorption, metabolism and activity at the platelet may interfere with its 
      antiplatelet actions. Further, proton pump inhibitors (PPI) may interfere with 
      clopidogrel's actions by functionally reducing the ability of CYP2C19 to convert 
      clopidogrel to its active metabolite. By attenuating clopidogrel's actions, both 
      polymorphisms and drug interactions may increase the risk of thrombotic events 
      during clopidogrel therapy. This review will explore the current evidence 
      relating to the association between PPIs, genetic polymorphisms and poor response 
      to clopidogrel. Routine genetic testing cannot be recommended for patients 
      receiving dual antiplatelet therapy (DAPT). However, it may have a role for 
      patients with an episode of stent thrombosis, prior to planned high-risk stenting 
      or major bleeding. Regarding concomitant clopidogrel and PPI therapy, it is 
      recommended that only patients with previous gastrointestinal (GI) bleeding or 
      multiple risk factors for GI bleeding should be prescribed gastroprotection. This 
      is due to the uncertainty surrounding the clinical significance of this 
      interaction given the discordant biochemical and clinical data, conflicting 
      results from observational studies and the limitations of the COGENT study. 
      Pantoprazole seems least likely to interact with clopidogrel and most suitable 
      for use in patients receiving DAPT.
FAU - Fernando, H
AU  - Fernando H
AD  - Department of Cardiovascular Medicine, Alfred Hospital/Baker IDI Heart and 
      Diabetes Institute, Melbourne, Victoria, Australia.
FAU - Dart, A M
AU  - Dart AM
FAU - Peter, K
AU  - Peter K
FAU - Shaw, J A
AU  - Shaw JA
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20110505
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - A74586SNO7 (Clopidogrel)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP2C19 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
RN  - OM90ZUW7M1 (Ticlopidine)
SB  - IM
MH  - Acute Coronary Syndrome/*therapy
MH  - Aryl Hydrocarbon Hydroxylases/genetics/*metabolism
MH  - *Blood Vessel Prosthesis Implantation
MH  - Clopidogrel
MH  - Coronary Thrombosis/prevention & control
MH  - Cytochrome P-450 CYP2C19
MH  - Drug Interactions
MH  - Enzyme Activation/drug effects
MH  - Genetic Testing
MH  - Humans
MH  - Platelet Aggregation Inhibitors/therapeutic use
MH  - Polymorphism, Genetic
MH  - *Postoperative Complications
MH  - Proton Pump Inhibitors/*pharmacology/therapeutic use
MH  - Ticlopidine/analogs & derivatives/metabolism/therapeutic use
MH  - Treatment Outcome
EDAT- 2011/05/06 06:00
MHDA- 2011/10/28 06:00
CRDT- 2011/05/06 06:00
PHST- 2010/11/10 00:00 [received]
PHST- 2011/03/14 00:00 [accepted]
PHST- 2011/05/06 06:00 [entrez]
PHST- 2011/05/06 06:00 [pubmed]
PHST- 2011/10/28 06:00 [medline]
AID - 10-11-0715 [pii]
AID - 10.1160/TH10-11-0715 [doi]
PST - ppublish
SO  - Thromb Haemost. 2011 Jun;105(6):933-44. doi: 10.1160/TH10-11-0715. Epub 2011 May 
      5.